Correction: Development of a novel X-ray fluorescence instrument equipped with a noble gas filter.

Correction for 'Development of a novel X-ray fluorescence instrument equipped with a noble gas filter' by Tsugufumi Matsuyama et al., Analyst, 2024, https://doi.org/10.1039/d4an00122b.

Development of a novel X-ray fluorescence instrument equipped with a noble gas filter.

In X-ray fluorescence (XRF) analysis, which has been used to analyze elements in various samples, it is important to decrease the background (BG) intensity. Generally, BG signals are reduced by inserting metal foils of various types and thicknesses between the X-ray tube and sample as primary X-ray filters. In this study, we developed a unique gas filter-XRF (GF-XRF) instrument to easily reduce the BG effect by changing the pressure of the gas to ensure that the absorption edge of the gas element is slightly lower than the energy of the XRF peak of the target element. The advantage of using a gas is that the gas pressure can be altered easily. To evaluate the performance of this instrument, Ti and Zr were selected as target elements, and Ar and Kr were selected as the filtering gases. When the XRF spectra of the Ti sample were recorded using the Ar gas filter, as the Ar gas pressure increased, the background signal in the energy region of the Ti Kα peak decreased, resulting in an increase in the signal-to-noise ratio (SNR) of that peak. When the Kr gas filter was used, both the SNR and the minimum detection limit of Zr improved. These results demonstrate that the unique GF-XRF instrument is useful for high-sensitivity analyses.

X-ray-Fluorescence-Based Screening Method for Uranium in Contaminated Brackish Water Using Graphene Oxide Nanosheets.

In the event of uranium release into the environment due to an accident, confirming the presence of uranium contamination is difficult because uranium is a naturally occurring element. In this study, we developed a method based on X-ray fluorescence (XRF) for the facile screening of uranium in brackish water samples in the event of an accident in a coastal area. Graphene oxide nanosheets were added to uncontaminated brackish water sampled from different sites to adsorb the uranium present in the samples, if any. The graphene oxide nanosheets were then collected using a membrane filter and analyzed using XRF. The results revealed that the signal intensity of the U Lα peak was proportional to the salinity. Hence, uranium contamination could be confirmed when the intensity of the U Lα peak was significantly greater than that derived from the background uranium content, as estimated from the salinity value. Thus, in the event of an accident, the salinity of the collected brackish water should be measured, and XRF analysis should be performed using our developed method. This method is useful for screening brackish water for uranium contamination.

Rapid detection of plutonium contamination with and without uranium contamination in wounds by x-ray fluorescence.

In the event of an accident at a nuclear fuel handling facility, the wounds of affected workers may be contaminated with plutonium. The current approach for identifying plutonium contamination is by detecting α-particles in the blood stream. However, the applicability of this approach is impeded due to the α-particles being easily shielded by the bodily fluid components. In this study, we investigate a contamination testing method for such cases that involves the collection of blood with a small piece of filter paper, sealing the sample with thin films, and performing x-ray fluorescence analysis. Our previous study on collecting uranium-contaminated blood with filter paper and performing x-ray fluorescence analysis revealed that the effects arising from blood components could be completely removed by peak fitting, and thus water instead of blood was used as a solvent here. Samples containing various amounts of plutonium as well as samples with 150 Bq of plutonium and uranium were prepared with a mass ratio of 0 to 500 times greater than that of plutonium. x-ray fluorescence measurements showed a high linearity and reproducibility of the Pu Lα peak intensity and plutonium radioactivity, and it was clarified that the signal intensity of the Pu Lα peak did not depend on the amount of coexisting uranium. This method will allow for the simple and rapid assessment of plutonium contamination in wounds.

Development of Methods to Evaluate Several Levels of Uranium Concentrations in Drainage Water Using Total Reflection X-Ray Fluorescence Technique.

As a country's law stipulates the effluent standard uranium concentration in drainage water, the uranium concentration must be determined when drainage water is released from a uranium handling facility, such as the Fukushima Daiichi nuclear power plant. The maximum allowable limit for uranium release at each facility is defined taking into consideration the situation of the facility, such as 1/10 to 1/100 of this effluent standard value. Currently, the uranium concentration of drainage water is commonly determined by α-particle spectrometry, in which several liters of drainage water must be evaporated, requiring about half of a day followed by 2-3 h of measurements, due to the low specific radioactivity of uranium. This work proposes a new methodology for the rapid and simple measurement of several levels of uranium in drainage water by a total reflection X-ray fluorescence (TXRF) analysis. Using a portable device for TXRF measurements was found to enable measurements with 1/10 the sensitivity of the effluent standard value by 10 times condensation of the uranium-containing sample solution; a benchtop device is useful to measure uranium concentrations <1/100 of the effluent standard value. Therefore, the selective usage of methods by a portable and benchtop devices allows for screening and precise evaluation of uranium concentrations in drainage water.

Rapid detection of heavy elements in blood extracted from wounds using x-ray fluorescence analysis.

In radiation emergency situations involving persons having plutonium (Pu)-contaminated wounds, rapid assessment of the degree of Pu contamination is required to determine the appropriate course of treatment. Currently, rapid on-site detection of Pu is usually performed by analysis of α-particles emitted from the adhesive tape peeled off the wound. However, the detection of α-particles is difficult, especially in traumatic skin lesions with oozing blood, because of the low permeability of α-particles in blood. Therefore, we focused on x-ray fluorescence (XRF) analysis because x-rays easily pass through several millimetres of blood. In this study, we developed a new methodology for the rapid detection of heavy elements in wounds based on XRF analysis of the contaminated blood collected by gauze patch and filter paper, using stable lead (Pb) as a model contaminant substitute for Pu. Mouse blood samples contaminated with Pb were dropped on gauze patches or absorbed by filter papers and were subjected to XRF measurement. Small pieces of filter paper served as more suitable extraction materials than gauze patches because the entire amount of blood absorbed could be measured. When we used filter paper, the signal intensity of the Pb Lα peak was proportional to the Pb concentration in the blood. With a measurement time of 30 s, the minimum detection limit of Pb in blood collected by filter paper was 2.4 ppm.

L Band EPR Tooth Dosimetry for Heavy Ion Irradiation.

Electron Paramagnetic Resonance (EPR) tooth dosimetry is being developed as a device to rapidly assess large populations that were potentially exposed to radiation during a major radiation accident or terrorist event. While most exposures are likely to be due to fallout and therefore involve low linear energy transfer (LET) radiation, there is also a potential for exposures to high LET radiation, for which the effect on teeth has been less well characterized by EPR. Therefore, the aim of this paper is to acquire fundamental response curves for high LET radiation in tooth dosimetry using L band EPR. For this purpose, we exposed human teeth to high energy carbon ions using the heavy ion medical accelerator in Chiba at the National Institute of Radiological Sciences. The primary findings were that EPR signals for carbon ion irradiation were about one-tenth the amplitude of the response to the same dose of 150 kVp X-rays.

Decline in intertidal biota after the 2011 Great East Japan Earthquake and Tsunami and the Fukushima nuclear disaster: field observations.

In 2011, 2012, and 2013, in the intertidal zones of eastern Japan, we investigated the ecological effects of the severe accident at the Fukushima Daiichi Nuclear Power Plant that accompanied the 2011 Great East Japan Earthquake and Tsunami. The number of intertidal species decreased significantly with decreasing distance from the power plant, and no rock shell (Thais clavigera) specimens were collected near the plant, from Hirono to Futaba Beach (a distance of approximately 30 km) in 2012. The collection of rock shell specimens at many other sites hit by the tsunami suggests that the absence of rock shells around the plant in 2012 might have been caused by the nuclear accident in 2011. Quantitative surveys in 2013 showed that the number of species and population densities in the intertidal zones were much lower at sites near, or within several kilometers south of, the plant than at other sites and lower than in 1995, especially in the case of Arthropoda. There is no clear explanation for these findings, but it is evident that the intertidal biota around the power plant has been affected since the nuclear accident.

PREDICTIVE FACTORS OF THE INITIAL TREATMENT FOR 207 BLUNT RENAL TRAUMA CASES BASED ON THE CLASSIFICATION FOR RENAL INJURY OF JAPANESE ASSOCIATION FOR THE SURGERY OF TRAUMA 2008's VERSION.

(Objective) We retrospectively investigated the applicability of the Japanese Association for the Surgery of Trauma (JAST) classification version 2008 for renal injuries as predictive factors of the initial treatment for 207 blunt renal injury cases. (Materials and methods) We reviewed 207 patients between 1982 and 2013 who were admitted to our institution with blunt renal trauma. Patients were classified as conservative management group, immediate transcatheter arterial embolization (TAE) group, and immediate nephrectomy group by initial treatment. We retrospectively assessed several parameters including JAST criteria version 2008 type of renal injury (type), severity of hematoma (H factor) and extravasation of urine (U factor), the shock on arrival, associated abdominal injuries, serum hemoglobin levels, and macrohematuria as predicting factors of initial treatment of blunt renal trauma. (Result) TypeIII and PV injuries, H2 factor and associated non-renal abdominal injuries were predictive factors of immediate nephrectomy (p=0.001, p=0.000, p=0.003). TypeIII and PV injuries and H2 factor were predictive factors of immediate TAE. Both of H2 and U2 factors were significant predictors of immediate nephrectomy in patients with typeIII injury. H factor was a significantly predictive factor of immediate TAE in patients with typeI/II injuries (p=0.040). The rate of immediate TAE has been increasing but the rate of partial nephrectomy except for nephrectomy has been decreasing since the year 2007 when TAE was immediately available in our hospital. (Conclusion) The type category and severity of hematoma of JAST classification version 2008 would be predictive factors of initial management of blunt renal injuries. Patients with typeIII injuries and both of H2 and U2 factors, can be adapted to immediate nephrectomy. Patients with typeI/II and H2 factors can be adapted to immediate TAE.

High-throughput screening with nanoimprinting 3D culture for efficient drug development by mimicking the tumor environment.

Anti-cancer drug development typically utilizes high-throughput screening with two-dimensional (2D) cell culture. However, 2D culture induces cellular characteristics different from tumors in vivo, resulting in inefficient drug development. Here, we report an innovative high-throughput screening system using nanoimprinting 3D culture to simulate in vivo conditions, thereby facilitating efficient drug development. We demonstrated that cell line-based nanoimprinting 3D screening can more efficiently select drugs that effectively inhibit cancer growth in vivo as compared to 2D culture. Metabolic responses after treatment were assessed using positron emission tomography (PET) probes, and revealed similar characteristics between the 3D spheroids and in vivo tumors. Further, we developed an advanced method to adopt cancer cells from patient tumor tissues for high-throughput drug screening with nanoimprinting 3D culture, which we termed Cancer tissue-Originated Uniformed Spheroid Assay (COUSA). This system identified drugs that were effective in xenografts of the original patient tumors. Nanoimprinting 3D spheroids showed low permeability and formation of hypoxic regions inside, similar to in vivo tumors. Collectively, the nanoimprinting 3D culture provides easy-handling high-throughput drug screening system, which allows for efficient drug development by mimicking the tumor environment. The COUSA system could be a useful platform for drug development with patient cancer cells.

Methodology using a portable X-ray fluorescence device for on-site and rapid evaluation of heavy-atom contamination in wounds: a model study for application to plutonium contamination.

Workers decommissioning the Fukushima-Daiichi nuclear power plant damaged from the Great East Japan Earthquake and resulting tsunami are at risk of injury with possible contamination from radioactive heavy atoms including actinides, such as plutonium. We propose a new methodology for on-site and rapid evaluation of heavy-atom contamination in wounds using a portable X-ray fluorescence (XRF) device. In the present study, stable lead was used as the model contaminant substitute for radioactive heavy atoms. First, the wound model was developed by placing a liquid blood phantom on an epoxy resin wound phantom contaminated with lead. Next, the correlation between the concentration of contaminant and the XRF peak intensity was formulated considering the thickness of blood exiting the wound. Methods to determine the minimum detection limit (MDL) of contaminants at any maximal equivalent dose to the wound by XRF measurement were also established. For example, in this system, at a maximal equivalent dose of 16.5 mSv to the wound and blood thickness of 0.5 mm, the MDL value for lead was 1.2 ppm (3.1 nmol). The radioactivity of 239Pu corresponding to 3.1 nmol is 1.7 kBq, which is lower than the radioactivity of 239Pu contaminating puncture wounds in previous severe accidents. In conclusion, the established methodology could be beneficial for future development of a method to evaluate plutonium contamination in wounds. Highlights: Methodology for evaluation of heavy-atom contamination in a wound was established. A portable X-ray fluorescence device enables on-site, rapid and direct evaluation. This method is expected to be used for evaluation of plutonium contamination in wounds.

Controlled administration of penicillamine reduces radiation exposure in critical organs during 64Cu-ATSM internal radiotherapy: a novel strategy for liver protection.

PURPOSE: (64)Cu-diacetyl-bis (N (4)-methylthiosemicarbazone) ((64)Cu-ATSM) is a promising theranostic agent that targets hypoxic regions in tumors related to malignant characteristics. Its diagnostic usefulness has been recognized in clinical studies. Internal radiotherapy (IRT) with (64)Cu-ATSM is reportedly effective in preclinical studies; however, for clinical applications, improvements to reduce radiation exposure in non-target organs, particularly the liver, are required. We developed a strategy to reduce radiation doses to critical organs while preserving tumor radiation doses by controlled administration of copper chelator penicillamine during (64)Cu-ATSM IRT. METHODS: Biodistribution was evaluated in HT-29 tumor-bearing mice injected with (64)Cu-ATSM (185 kBq) with or without oral penicillamine administration. The appropriate injection interval between (64)Cu-ATSM and penicillamine was determined. Then, the optimal penicillamine administration schedule was selected from single (100, 300, and 500 mg/kg) and fractionated doses (100 mg/kg×3 at 1- or 2-h intervals from 1 h after (64)Cu-ATSM injection). PET imaging was performed to confirm the effect of penicillamine with a therapeutic (64)Cu-ATSM dose (37 MBq). Dosimetry analysis was performed to estimate human absorbed doses. RESULTS: Penicillamine reduced (64)Cu accumulation in the liver and small intestine. Tumor uptake was not affected by penicillamine administration at 1 h after (64)Cu-ATSM injection, when radioactivity was almost cleared from the blood and tumor uptake had plateaued. Of the single doses, 300 mg/kg was most effective. Fractionated administration at 2-h intervals further decreased liver accumulation at later time points. PET indicated that penicillamine acts similarly with the therapeutic (64)Cu-ATSM dose. Dosimetry demonstrated that appropriately scheduled penicillamine administration reduced radiation doses to critical organs (liver, ovaries, and red marrow) below tolerance levels. Laxatives reduced radiation doses to the large intestine. CONCLUSIONS: We developed a novel strategy to reduce radiation exposure in critical organs during (64)Cu-ATSM IRT, thus promoting its clinical applications. This method could be beneficial for other (64)Cu-labeled compounds.

Fatty acid synthase is a key target in multiple essential tumor functions of prostate cancer: uptake of radiolabeled acetate as a predictor of the targeted therapy outcome.

Fatty acid synthase (FASN) expression is elevated in several cancers, and this over-expression is associated with poor prognosis. Inhibitors of FASN, such as orlistat, reportedly show antitumor effects against cancers that over-express FASN, making FASN a promising therapeutic target. However, large variations in FASN expression levels in individual tumors have been observed, and methods to predict FASN-targeted therapy outcome before treatment are required to avoid unnecessary treatment. In addition, how FASN inhibition affects tumor progression remains unclear. Here, we showed the method to predict FASN-targeted therapy outcome using radiolabeled acetate uptake and presented mechanisms of FASN inhibition with human prostate cancer cell lines, to provide the treatment strategy of FASN-targeted therapy. We revealed that tumor uptake of radiolabeled acetate reflected the FASN expression levels and sensitivity to FASN-targeted therapy with orlistat in vitro and in vivo. FASN-targeted therapy was noticeably effective against tumors with high FASN expression, which was indicated by high acetate uptake. To examine mechanisms, we established FASN knockdown prostate cancer cells by transduction of short-hairpin RNA against FASN and investigated the characteristics by analyses on morphology and cell behavior and microarray-based gene expression profiling. FASN inhibition not only suppressed cell proliferation but prevented pseudopodia formation and suppressed cell adhesion, migration, and invasion. FASN inhibition also suppressed genes involved in production of intracellular second messenger arachidonic acid and androgen hormones, both of which promote tumor progression. Collectively, our data demonstrated that uptake of radiolabeled acetate is a useful predictor of FASN-targeted therapy outcome. This suggests that [1-(11)C]acetate positron emission tomography (PET) could be a powerful tool to accomplish personalized FASN-targeted therapy by non-invasive visualization of tumor acetate uptake and selection of responsive tumors. FASN-targeted therapy could be an effective treatment to suppress multiple steps related to tumor progression in prostate cancers selected by [1-(11)C]acetate PET.

Photo-excitation of carotenoids causes cytotoxicity via singlet oxygen production.

Carotenoids, natural pigments widely distributed in algae and plants, have a conjugated double bond system. Their excitation energies are correlated with conjugation length. We hypothesized that carotenoids whose energy states are above the singlet excited state of oxygen (singlet oxygen) would possess photosensitizing properties. Here, we demonstrated that human skin melanoma (A375) cells are damaged through the photo-excitation of several carotenoids (neoxanthin, fucoxanthin and siphonaxanthin). In contrast, photo-excitation of carotenoids that possess energy states below that of singlet oxygen, such as ß-carotene, lutein, loroxanthin and violaxanthin, did not enhance cell death. Production of reactive oxygen species (ROS) by photo-excited fucoxanthin or neoxanthin was confirmed using a reporter assay for ROS production with HeLa Hyper cells, which express a fluorescent indicator protein for intracellular ROS. Fucoxanthin and neoxanthin also showed high cellular penetration and retention. Electron spin resonance spectra using 2,2,6,6-tetramethil-4-piperidone as a singlet oxygen trapping agent demonstrated that singlet oxygen was produced via energy transfer from photo-excited fucoxanthin to oxygen molecules. These results suggest that carotenoids such as fucoxanthin, which are capable of singlet oxygen production through photo-excitation and show good penetration and retention in target cells, are useful as photosensitizers in photodynamic therapy for skin disease.

Radiolabeled Cu-ATSM as a novel indicator of overreduced intracellular state due to mitochondrial dysfunction: studies with mitochondrial DNA-less ρ0 cells and cybrids carrying MELAS mitochondrial DNA mutation.

OBJECTIVES: Radiolabeled Cu-diacetyl-bis (N(4)-methylthiosemicarbazone) (*Cu-ATSM), including (60/62/64)Cu-ATSM, is a potential imaging agent of hypoxic tumors for positron emission tomography (PET). We have reported that *Cu-ATSM is trapped in tumor cells under intracellular overreduced states, e.g., hypoxia. Here we evaluated *Cu-ATSM as an indicator of intracellular overreduced states in mitochondrial disorders using cell lines with mitochondrial dysfunction. METHODS: Mitochondrial DNA-less ρ(0)206 cells; the parental 143B human osteosarcoma cells; the cybrids carrying mutated mitochondria from a patient of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) (2SD); and that carrying wild-type one (2SA) were used. Cells were treated under normoxia or hypoxia, and (64)Cu-ATSM uptake was examined to compare it with levels of biological reductant NADH and NADPH. RESULTS: ρ(0)206 cells showed higher (64)Cu-ATSM uptake than control 143B cells under normoxia, whereas (64)Cu-ATSM uptake was not significantly increased under hypoxia in ρ(0)206 cells. Additionally, (64)Cu-ATSM uptake showed correlate change to the NADH and NADPH levels, but not oxygenic conditions. 2SD cells showed increased (64)Cu-ATSM uptake under normoxia as compared with the control 2SA, and (64)Cu-ATSM uptake followed NADH and NADPH levels, but not oxygenic conditions. CONCLUSIONS: (64)Cu-ATSM accumulated in cells with overreduced states due to mitochondrial dysfunction, even under normoxia. We recently reported that (62)Cu-ATSM-PET can visualize stroke-like episodes maintaining oxygen supply in MELAS patients. Taken together, our data indicate that *Cu-ATSM uptake reflects overreduced intracellular states, despite oxygenic conditions; thus, *Cu-ATSM would be a promising marker of intracellular overreduced states for disorders with mitochondrial dysfunction, such as MELAS, Parkinson's disease and Alzheimer's disease.

The use of nanoimprinted scaffolds as 3D culture models to facilitate spontaneous tumor cell migration and well-regulated spheroid formation.

Two-dimensional (2D) cell cultures are essential for drug development and tumor research. However, the limitations of 2D cultures are widely recognized, and a better technique is needed. Recent studies have indicated that a strong physical contact between cells and 2D substrates induces cellular characteristics that differ from those of tumors growing in vivo. 3D cell cultures using various substrates are then developing; nevertheless, conventional approaches have failed in maintenance of cellular proliferation and viability, uniformity, reproducibility, and/or simplicity of these assays. Here, we developed a 3D culture system with inorganic nanoscale scaffolding using nanoimprinting technology (nano-culture plates), which reproduced the characteristics of tumor cells growing in vivo. Diminished cell-to-substrate physical contact facilitated spontaneous tumor cell migration, intercellular adhesion, and multi-cellular 3D-spheroid formation while maintaining cellular proliferation and viability. The resulting multi-cellular spheroids formed hypoxic core regions similar to tumors growing in vivo. This technology allows creating uniform and highly-reproducible 3D cultures, which is easily applicable for microscopic and spectrophotometric assays, which can be used for high-throughput/high-content screening of anticancer drugs and should accelerate discovery of more effective anticancer therapies.

Internal radiotherapy with copper-64-diacetyl-bis (N4-methylthiosemicarbazone) reduces CD133+ highly tumorigenic cells and metastatic ability of mouse colon carcinoma.

INTRODUCTION: (64)Cu-diacetyl-bis (N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) is an imaging agent for positron emission tomography (PET) that targets hypoxic tumors. (64)Cu-ATSM is also reported to be a potential agent for internal radiotherapy. In a mouse colon carcinoma (Colon-26) model, we have shown that (64)Cu-ATSM preferentially localizes in intratumoral regions with a high density of CD133(+) cells, which show characteristics of cancer stem cells or cancer stem cell-like cells (collectively referred here as CSCs). In this study, we evaluated the therapeutic effect of (64)Cu-ATSM in relation to CD133 expression using this model. METHODS: Systemic administration of 37 MBq (64)Cu-ATSM or saline was conducted twice within a 1-week interval to mice bearing 1-week-old Colon-26 tumors (days 0-7). At day 19, tumor size measurement, flow cytometry analysis and experimental lung metastatic assay were performed. The therapeutic effect of (64)Cu-ATSM on sorted CD133(+) and CD133(-) Colon-26 cells was also examined in vitro. RESULTS: In vivo studies showed that (64)Cu-ATSM treatment inhibited tumor growth. The percentage of CD133(+) cells and metastatic ability in (64)Cu-ATSM treated tumors was decreased compared with that in control animals. In vitro studies demonstrated that (64)Cu-ATSM accumulated in cells under hypoxic conditions and incorporation of (64)Cu-ATSM under hypoxia caused cell death in both CD133(+) and CD133(-) cells in a similar extent. CONCLUSIONS: (64)Cu-ATSM administration reduced tumor volume as well as the percentage of CD133(+) cells and the metastatic ability of Colon-26 tumors. Together with our data, it is suggested that (64)Cu-ATSM accumulates in regions high in CD133(+) highly tumorigenic cells and kills such regions by radiation, resulting in a decrease of the percentage of CD133(+) cells.

Predictive value of a flat inferior vena cava on initial computed tomography for hemodynamic deterioration in patients with blunt torso trauma.

BACKGROUND: We aimed to investigate the value of the diameter of the inferior vena cava (IVC) on initial computed tomography (CT) to predict hemodynamic deterioration in patients with blunt torso trauma. METHODS: We reviewed the initial CT scans, taken after admission to emergency room (ER), of 114 patients with blunt torso trauma who were consecutively admitted during a 24-month period. We measured the maximal anteroposterior and transverse diameters of the IVC at the level of the renal vein. Flat vena cava (FVC) was defined as a maximal transverse to anteroposterior ratio of less than 4:1. According to the hemodynamic status, the patients were categorized into three groups. Patients with hemodynamic deterioration after the CT scans were defined as group D (n = 37). The other patients who remained hemodynamically stable after the CT scans were divided into two groups: patients who were hemodynamically stable on ER arrival were defined as group S (n = 60) and those who were in shock on ER arrival and responded to the fluid resuscitation were defined as group R (n = 17). RESULTS: The anteroposterior diameter of the IVC in group D was significantly smaller than those in groups R and S (7.6 mm ± 4.4 mm, 15.8 mm ± 5.5 mm, and 15.3 mm ± 4.2 mm, respectively; p < 0.05). Of the 93 patients without FVC, 16 (17%) were in group D, 14 (15%) required blood transfusion, and 8 (9%) required intervention. However, of the 21 patients with FVC, all patients were in group D, 20 (95%) required blood transfusion, and 17 (80%) required intervention. The patients with FVC had higher mortality (52%) than the other patients (2%). CONCLUSION: In cases of blunt torso trauma, patients with FVC on initial CT may exhibit hemodynamic deterioration, necessitating early blood transfusion and therapeutic intervention.

Copper-64-diacetyl-bis (N4-methylthiosemicarbazone) accumulates in rich regions of CD133+ highly tumorigenic cells in mouse colon carcinoma.

INTRODUCTION: (64)Cu-diacetyl-bis (N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) is a potential imaging agent of hypoxic tumor for use with PET. Recent literature demonstrated that cancer cells expressing CD133, which is a frequently used marker for so-called cancer stem cells or cancer stem cell-like cells (collectively referred to here as CSCs), contribute to tumor's therapeutic resistance and metastasis ability. Culturing under hypoxia is also reported to enlarge the proportion of CD133(+) cells, which would indicate survival advantage of CD133(+) cells under hypoxia. Here, we investigated the relationships between (64)Cu-ATSM accumulation and existence of CD133(+) cells using mouse colon carcinoma (colon-26) tumor. METHODS: Intratumor distribution of (64)Cu-ATSM and (18)F-fluorodeoxyglucose ((18)FDG) was compared with immunohistochemical staining for CD133 with a colon-26 model. In vitro characterization of CD133(+) colon-26 cells was also performed. RESULTS: In colon-26 tumors, (64)Cu-ATSM localized preferentially in regions with a high density of CD133(+) cells. The percentage of CD133(+) cells was 11-fold higher in (64)Cu-ATSM high-uptake regions compared with (18)FDG high- (but (64)Cu-ATSM low-) uptake regions. CD133(+) colon-26 cells showed characteristics previously linked with CSCs in other cancer cell lines, such as high colony-forming ability, high tumor-initiating ability and enrichment under hypoxic cultivation. The proportion of CD133(+) cells was enlarged by culturing under glucose starvation as well as hypoxia, and (64)Cu-ATSM uptake was increased under such conditions. CONCLUSIONS: Our findings showed that, in colon-26 tumors, (64)Cu-ATSM accumulates in rich regions of CD133(+) cells with characteristics of CSCs. Therefore (64)Cu-ATSM could be a potential imaging agent for rich regions of CD133(+) cells, associated with CSCs, within tumors.